A clinical study to confirm the doses of selexipag to be used in children with pulmonary arterial hypertensio
- Conditions
- Pulmonary arterial hypertensionMedDRA version: 20.0Level: PTClassification code 10064911Term: Pulmonary arterial hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2018-000145-39-HU
- Lead Sponsor
- Actelion Pharmaceuticals Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 55
1. Signed and dated informed consent by the parent(s) or Legally authorized representative(s) AND assent from developmentally capable children.
2. Males or females between = 2 and < 18 years of age with weight = 9 kg.
3. PAH diagnosis confirmed by documented historical right heart catheterization (RHC) performed at any time before subject’s enrollment
4. PAH with one of the following etiologies:
• idiopathic (iPAH),
• heritable (hPAH),
• associated with congenital heart disease (CHD):
– PAH with co-incidental CHD
– Post-operative PAH (persisting/ recurring/ developing = 6 months after repair of CHD)
• Drug or toxin-induced
• PAH associated with HIV
• PAH associated with connective tissue disease
5. Word Health Organizaition functional class (WHO FC) II to III.
6. Subjects treated with an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type 5 (PDE-5) inhibitor provided that the treatment dose(s) has been stable for at least 3 months prior to enrollment, or patients who are not candidates for these therapies.
7. Females of childbearing potential must have a negative pregnancy test at Screening and at Enrollment, and must agree to undertake monthly pregnancy tests, and to use a reliable method of contraception (if sexually active) from screening up to study drug discontinuation plus 30 days (EOS).
Are the trial subjects under 18? yes
Number of subjects for this age range: 55
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Etiology
1. Subjects with PAH due to portal hypertension, schistosomiasis, pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis.
2. Subjects with PAH associated with Eisenmenger syndrome.
3. Subjects with moderate to large left-to-right shunts.
4. Subjects with cyanotic congenital cardiac lesions such as transposition of the great arteries, truncus arteriosus, univentricular heart or pulmonary atresia with ventricular septal defect, as well as subjects with Fontan-palliation.
5. Subjects with pulmonary hypertension due to lung disease (e.g., bronchopulmonary dysplasia).
Treatment and intervention
6. Previous treatment with Uptravi (selexipag) within 2 weeks prior to enrollment.
7. Subjects having received prostacyclin (epoprostenol) or prostacyclin analogs (i.e., treprostinil, iloprost, beraprost) within 2 months prior to enrollment or are scheduled to receive any of these compounds during the trial.
8. Treatment with another investigational drug within 4 weeks prior to enrollment.
9. History, or current suspicion of intussusception or ileus or gastrointestinal obstruction as per investigator’s judgment.
Baseline abnormalities
10. Uncontrolled thyroid disease as per investigator judgment.
11. Hemoglobin or hematocrit < 75% of the lower limit of normal range.
12. Known severe or moderate hepatic impairment.
13. Clinical signs of hypotension that in the investigator’s judgment would preclude initiation of a PAH-specific therapy.
14. Subjects with severe renal insufficiency (estimated creatinine clearance < 30 mL/min or serum creatinine > 221 µmol/L).
Other categories
15. Known hypersensitivity to the investigational treatment or to any of the excipients of the drug formulations.
16. History or clinical evidence of any disease and/or existence of any surgical or medical condition which might interfere with the absorption, distribution, metabolism or excretion of the study treatment(s) (e.g., cholecystectomy).
17. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of the study is to confirm the selexipag starting dose(s), selected based on pharmacokinetic (PK) extrapolation from adults, which leads to similar exposures as adult doses in children from = 2 to < 18 years of age, with pulmonary arterial hypertension (PAH), by investigating the PK of selexipag and its active metabolite ACT-333679 in this population.;Secondary Objective: To evaluate the safety and tolerability of selexipag in children from = 2 to < 18 years of age with PAH.;Primary end point(s): Primary pharmacokinetic (PK) endpoint: <br>- Model-based exposure (AUCt,ss, combined) of selexipag and ACT-333679 corrected for their potency, determined during the 12 weeks up-titration period.;Timepoint(s) of evaluation of this end point: - PK sampling at Weeks 1, 2, 4, 6 and 12
- Secondary Outcome Measures
Name Time Method